1. The Field of the Invention
The present invention relates to spargers incorporated into a flexible bag.
2. The Relevant Technology
Spargers are commonly used in bioreactors for delivering controlled volumes of gas to a growth media containing cells. In part, the gas is used to control the partial pressure of oxygen within the growth media and to control the pH and other perimeters of the growth media so that the conditions are optimal for cell growth. Spargers typically comprise a hollow metal ring having a hose coupled thereto. The ring is formed from a sintered metal so that the ring is porous. The ring is manually positioned at the bottom of a container with the hose extending up through a port at the top of the container. During operation, pressurized gas is delivered to the ring through the hose. The gas then permeates out through the metal ring so as to enter the media in the form of small bubbles. As the bubbles travel up through the media, at least a portion of the gas becomes entrained within the media. Other c′ 9 conventional spargers comprise a section of stainless steel tubing that is bent into a ring with small diameter holes positioned along the curved length thereof.
Although conventional spargers are useful in delivering gas to the media, they have a number of shortcomings. For example, conventional spargers are relatively expensive to make and are thus designed to be reused. Reuse of a conventional sparger, however, requires that it be removed from the container and then cleaned and sterilized. In some situations, cleaning of the sparger can be difficult in that cell by-product, dead cells, and other particulate within the growth media can be lodged on or trapped within the sparger. Thus cleaning and sterilizing of the sparger can be both time consuming and expensive. Time and care must also be taken to properly position and seal the sparger within the container without contaminating the sparger or the container.
Furthermore, in conventional bioreactors it is necessary that the growth media containing the cells be continually mixed or suspended so that the properties of the growth media remain homogeneous. Conventional spargers can obstruct the flow of the fluid which can produce dead spots where the cells die. Furthermore, the cells can be caught on or by the sparger which can damage or kill the cells. In addition, the spargers must be carefully designed and positioned so that they do not obstruct the mixing system.
Some current bioreactors comprise a flexible bag that is disposed within a rigid support housing. The cell culture is grown within the sterile compartment of the flexible bag. In an attempt to eliminate some of the above sparger problems, disposable spargers have been incorporated into the flexible bags. Such disposable spargers comprise a port having an enlarged annular flange welded to the inside of the bag and a tubular stem that projects from the flange to outside the bag. The stem bounds a passage that extends through the flange. A porous film overlays the flange inside of the bag so as to cover the passage and is welded around the perimeter edge of the flange. As a result, gas can be passed through the stem from outside the bag. The gas passes through the flange and then passes through the porous film where it enters the cell culture within the bag in the form of small bubbles. When the cell production is completed, the bag and associated sparger are simply disposed of.
Although the above flexible sparger eliminates some of the problems of conventional spargers, the new bag spargers also have their shortcomings. Most notably, the bag spargers only sparge at a relatively small, fixed location on the bag and are limited to only one size of gas bubbles. As such, bag spargers have limited or no adjustability with regard to sparging at different locations, flow rates, bubbles sizes, or combinations of the forgoing.
Accordingly, what is needed are spargers and container systems that can solve one or more of the above shortcomings.